There is a growing need for kidney transplantation in HIV-infected (HIV+) individuals as the prevalence of end- stage renal disease increases. Outcomes of transplant in HIV+ individuals with kidneys from HIV-uninfected (HIV-) donors are excellent. However, there is a profound organ shortage, with extremely long waiting times, and a higher waitlist mortality for HIV+ individuals in particular. Organs from HIV+ deceased donors (HIVD+) are a unique resource for HIV+ transplant candidates. By expanding the donor pool, use of organs from HIVD+ could have a significant public health impact and decrease wait times for everyone on the waitlist. This motivated the Congressional HOPE (HIV Organ Policy Equity) Act which now allows HIVD+ transplants for HIV+ recipients (R+) under research protocols. Potential risks of HIVD+ transplants include complications related to donor-to-recipient HIV superinfection (HIV-SI) and development of HIV-associated kidney disease after transplant. Preliminary experience with HIVD+ transplants in South Africa is encouraging, however, the experience cannot be generalized to the US due to population differences (race, age, sex, health care access), and disease differences (underlying kidney disease, HIV prevalence, subtype, opportunistic infections, access and resistance to antiretroviral therapy). To determine if HIVD+ kidney transplantation is safe and effective in the US, we propose HOPE in Action: A Prospective Multicenter, Clinical Trial of HIV+ Deceased Donor Kidney Transplants for HIV+ Recipients. We will compare transplant outcomes between HIV+ recipients who receive kidneys from HIV+ versus HIV- donors enrolling 80 in each group over 3 years at 16 transplant centers. Aim 1 is to compare differences in time to HIV-related complications and Aim 2 to compare incidence of HIV-related kidney disease. In Aim 3, we will characterize HIV-SI in blood and its association with clinical outcomes and in Aim 4 we will characterize changes in HIV reservoirs over time in participants receiving immunosuppressants of interest for HIV cure. Finally, establishment of a rich biorepository of tissue and blood from this unique cohort will provide an unprecedented opportunity for future mechanistic studies related to HIV persistence and pathogenesis. With support from NIAID (R34AI23023) over the past year, we have planned and designed the trial, assembling a team of experts in Transplant Surgery, HIV/Infectious Diseases, Nephrology, Epidemiology, Biostatistics, Pathology and Virology. We have partnered with the UNOS and OPTN in an ongoing study to identify and evaluate HIVD+ nationally (R01AI120938). In addition, we are coordinating a multicenter clinical pilot study and have performed the first-in-US HIVD+ kidney and liver transplants. The proposed clinical trial will determine whether the use of HIVD+ is safe and effective. If implemented, this practice could provide the largest expansion of the organ donor pool in the last decade, potentially saving thousands of lives of HIV+ and HIV-negative individuals.